New CRISPR–Cas systems from uncultivated microbes

Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

doi:10.1038/nature21059

Title: New CRISPR–Cas systems from uncultivated microbes

Journal Article · Thu Dec 22 00:00:00 EST 2016 · Nature (London)

DOI:https://doi.org/10.1038/nature21059· OSTI ID:1379729

Burstein, David ^[1]; Harrington, Lucas B. ^[2]; Strutt, Steven C. ^[2]; Probst, Alexander J. ^[1]; Anantharaman, Karthik ^[1]; Thomas, Brian C. ^[1]; Doudna, Jennifer A. ^[3]; Banfield, Jillian F. ^[4]

Univ. of California, Berkeley, CA (United States). Department of Earth and Planetary Sciences
Univ. of California, Berkeley, CA (United States). Department of Molecular and Cell Biology
Univ. of California, Berkeley, CA (United States). Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Innovative Genomics Initiative, and MBIB Division
Univ. of California, Berkeley, CA (United States). Department of Earth and Planetary Sciences and Department of Environmental Science, Policy, and Management

We present that CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Lastly, interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1379729

Journal Information:: Nature (London), Vol. 542, Issue 7640; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 335 works

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A new statistic for efficient detection of repetitive sequences Chen, Sijie; Chen, Yixin; Sun, Fengzhu Bioinformatics, Vol. 35, Issue 22 https://doi.org/10.1093/bioinformatics/btz262	journal	April 2019
Multiplex genome editing of microorganisms using CRISPR-Cas Adiego-Pérez, Belén; Randazzo, Paola; Daran, Jean Marc FEMS Microbiology Letters, Vol. 366, Issue 8 https://doi.org/10.1093/femsle/fnz086	journal	April 2019
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Gene editing in dermatology: Harnessing CRISPR for the treatment of cutaneous disease Baker, Catherine; Hayden, Matthew S. F1000Research, Vol. 9 https://doi.org/10.12688/f1000research.23185.2	journal	January 2020
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Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein Yan, Winston X.; Chong, Shaorong; Zhang, Huaibin Molecular Cell, Vol. 70, Issue 2 https://doi.org/10.1016/j.molcel.2018.02.028	journal	April 2018
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Harnessing “A Billion Years of Experimentation”: The Ongoing Exploration and Exploitation of CRISPR–Cas Immune Systems Klompe, Sanne E.; Sternberg, Samuel H. The CRISPR Journal, Vol. 1, Issue 2 https://doi.org/10.1089/crispr.2018.0012	journal	April 2018
EBI Metagenomics in 2017: enriching the analysis of microbial communities, from sequence reads to assemblies Mitchell, Alex L.; Scheremetjew, Maxim; Denise, Hubert Nucleic Acids Research, Vol. 46, Issue D1 https://doi.org/10.1093/nar/gkx967	journal	October 2017
CRISPR-Cas Genome Surgery in Ophthalmology DiCarlo, James E.; Sengillo, Jesse D.; Justus, Sally Translational Vision Science & Technology, Vol. 6, Issue 3 https://doi.org/10.1167/tvst.6.3.13	journal	May 2017
Correction to: CRISPR-like sequences in Helicobacter pylori and application in genotyping Bangpanwimon, Khotchawan; Sottisuporn, Jaksin; Mittraparp-arthorn, Pimonsri Gut Pathogens, Vol. 9, Issue 1 https://doi.org/10.1186/s13099-017-0221-x	journal	December 2017
Cas1 and Cas2 From the Type II-C CRISPR-Cas System of Riemerella anatipestifer Are Required for Spacer Acquisition He, Yang; Wang, Mingshu; Liu, Mafeng Frontiers in Cellular and Infection Microbiology, Vol. 8 https://doi.org/10.3389/fcimb.2018.00195	journal	June 2018
Candidate Phyla Radiation Roizmanbacteria From Hot Springs Have Novel and Unexpectedly Abundant CRISPR-Cas Systems Chen, Lin-Xing; Al-Shayeb, Basem; Méheust, Raphaël Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.00928	journal	May 2019
Genomic Characterization of a Novel Gut Symbiont From the Hadal Snailfish Lian, Chun-Ang; Yan, Guo-Yong; Huang, Jiao-Mei Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.02978	journal	January 2020
Genome Editing in Trees: From Multiple Repair Pathways to Long-Term Stability Bewg, William Patrick; Ci, Dong; Tsai, Chung-Jui Frontiers in Plant Science, Vol. 9 https://doi.org/10.3389/fpls.2018.01732	journal	November 2018
Seasonal Reproduction in Vertebrates: Melatonin Synthesis, Binding, and Functionality Using Tinbergen’s Four Questions ViviD, Dax; Bentley, George E. Molecules, Vol. 23, Issue 3 https://doi.org/10.3390/molecules23030652	journal	March 2018
“French Phage Network”—Second Meeting Report Torres-Barceló, Clara; Kaltz, Oliver; Froissart, Rémy Viruses, Vol. 9, Issue 4 https://doi.org/10.3390/v9040087	journal	April 2017
CRISPR Genome Engineering for Human Pluripotent Stem Cell Research Chaterji, Somali; Ahn, Eun Hyun; Kim, Deok-Ho Theranostics, Vol. 7, Issue 18 https://doi.org/10.7150/thno.18456	journal	January 2017
Allele-specific genome targeting in the development of precision medicine Wu, Junjiao; Tang, Beisha; Tang, Yu Theranostics, Vol. 10, Issue 7 https://doi.org/10.7150/thno.43298	journal	January 2020
Detection and variability analyses of CRISPR-like loci in the H. pylori genome Garcia-Zea, Jerson Alexander; de la Herran, Roberto; Rodriguez, Francisca Robles PeerJ Preprints https://doi.org/10.7287/peerj.preprints.27196v1	journal	September 2018

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